Title: Investigation of the modifying effects of vitamin A and hypoxic cell sensitizers in radiation carcinogenesis in mice

Abstract

The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed. In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100 g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. Mice were killed, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet. In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2 mg/g and 0.6 mg/g, were used either alone or in combination with 900 rad of gamma radiation in amore » fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased in the higher dose group (0.6 mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group.« less

@article{osti_5123210,
title = {Investigation of the modifying effects of vitamin A and hypoxic cell sensitizers in radiation carcinogenesis in mice},
author = {Mian, T.A.},
abstractNote = {The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed. In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100 g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. Mice were killed, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet. In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2 mg/g and 0.6 mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased in the higher dose group (0.6 mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = 1982,
month = 1
}

This thesis has examined the biological and biochemical basis by which excess selenium (Se) exerts anti-carcinogenic effects. The work has focused on three major points: 1) can Se affect hepatocarcinogenesis independent of alterations in carcinogen metabolism and if so, how. 2) does excess Se affect cell proliferation and if so, what stages of the mammalian cell cycle are affected. and 3) are alterations in cellular glutathione metabolism responsible for the observed cell damage and anti-carcinogenic effects of excess Se. The results presented in this thesis demonstrate that excess Se can decrease cell proliferation and this serves as a plausible explanationmore » for the decreased growth of pre-neoplastic lesions observed with high Se. Increased cellular GSSG or GSSG/GSH ratio may be responsible for the decreased proliferation. High SE may also enhance carcinogenesis if fed in conjuction with tumor promoters or if adaptive liver growth occurs in response to high Se.« less

Whole bacterial cells of high radiation resistance were injected into mice that were subjected to a lethal dose of irradiation. It was observed that cells injected into the peritoneal cavity of mice before or after irradiation protected some of them from a lethal dose of irradiation. The effect of extricts from the cells was then examined. The cytoplasmic and particulate material was isolated from R1 by sonication of whole cells and these were tested for their protective efficacy. Though both fraction protected mice from the lethal effects of radiation the particulate material gave better results. Cellular extracts of pigment materialmore » were examined for their protective ability as well as various other cellular extracted material. The sulfuric acid or petroleumn ether extracted cellular material gave the best results, Miescher's method for isolating nuclear material yielded material that was the most effective radiation protective material of the nuclear mnterials tested. Even though the nuclear material prepared by Miescher's method was crude, containing associated lipid, pigment and protein material, chemical analysis was performed. The results indicated more suifur than expected. The crude nuclear material was purified further by separating the lipid-pigment material from it. The lipid-pigment material of the nucleic acid extracted material appeared to be the protective fraction rather than the nucleic acid material. When purified still further by saponification or when the methyl derivative was prepared, the lipid portion had more protective properties than the pigmert material. The pigment-lipid material was also crudely separated on a silicic acid column and the first fractions that were removed (neutral fats and bound lipids) appeared to be the protective portion. (Dissertation Abstr., 24: No. 9, March« less